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Calcitonin gene-related peptide (CGRP) is a vasodilator neuropeptide that is expressed in a subgroup of small neurons in the dorsal root ganglion (DRG), trigeminal, and vagal ganglia, which respond to noxious, thermal, or visceral input. These peptidergic neurons use l-glutamate as their primary neurotransmitter and project to the dorsal horn, trigeminal nucleus caudalis, or nucleus of the solitary tract. CGRP, acting via a unique receptor complex, increases neurotransmitter release and neuronal responsiveness to noxious stimulation at all these levels, which leads to central sensitization underlying chronic pain states. CGRP can also be released antidromically in the periphery, eliciting vasodilation as a component of neurogenic inflammation. CGRP-containing pathways from the parabrachial nuclear complex (PBN) and posterior thalamus convey nociceptive and visceral sensation to the amygdala and the insular cortex. CGRP may be involved in the pathophysiology of inflammatory and neuropathic pain. Involvement of CGRP in migraine headache has led to the development of CGRP antagonists for treatment of this disorder. There are several reviews on these topics.1,–,11
CGRP AS A SENSORY NEUROTRANSMITTER
CGRP is a 37–amino acid peptide that is a member of the calcitonin family, which also includes calcitonin, amylin, and adrenomedullin. CGRP exists in 2 distinct isoforms: CGRPα (CGRP1), which is the product of alternative splicing of the calcitonin gene in neurons, and CGRPβ (CGRP2), which is encoded by a separate gene.1 These 2 CGRP peptides differ from each other by 3 amino acids and have so far proved to be indistinguishable in their biological activities. CGRP is widely expressed in the central and peripheral nervous systems1,12,–,15 and frequently coexists and interacts with other neurotransmitters.1 This review focuses on the distribution and functions of CGRP as a sensory neurotransmitter.
CGRP as neurotransmitter in primary afferents.
CGRP is expressed in a subset of small neurons in …
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